Antigen-antibody complexes play important roles in a variety of human systemic and cutaneous diseases. This laboratory studies how immune complexes are formed, how they cause tissue damage, and how they are cleared from the circulation. We have identified and partially characterized the immune complexes which exist in a variety of human diseases utilizing highly sensitive radioimmunoassays. We have developed a sensitive radioimmunoassay for the detection of IgA containing immune complexes. We have determined the antibody classes present in the immune complexes and examined the physiochemical characteristics of these complexes, as well as the reaction of these complexes with mediators of inflammation such as the complement system. We have examined the correlation between absolute levels of circulating immune complexes, the extent and severity of clinical disease, and reticuloendothelial system function. We have also examined the influence that certain genes of the major histocompatibility complex exert on immune function in vivo and in vitro in humans. Since immune complexes may activate the complement system and since the complement fragments C5a and C3a are thought to be important in the pathogenesis of the inflammatory response in cutaneous and systemic diseases, we have purified C5a and studied its in vivo and in vitro reactivity. Its in vivo role was assessed by the first in-depth analysis of the cutaneous reactivity of this complement fragment in man. We have also studied the ability of C5a and C3a to modulate cell surface receptors for immunoglobulin and complement on the surface of leukocytes. Increasing evidence indicates that human endothelial cells, under certain circumstances, can be induced to become immunologically competent. In order to evaluate the role endothelial cells in immune complex mediated vasculitis we have isolated human umbilical vein endothelial cells, grown them in cell culture, examined them for the presence of immunologically relevant cell surface antigens and receptors before and after stimulation with soluble mediators of immunoregulation.